Cell pathology tubes and associated cell processing methods

ABSTRACT

Cell tubes that can be used both for pathology collection and subsequent cell processing include a tube with a cell bed at a lower portion of the tube. The tube can include a base member that can be detachable from the tube body. The tubes can be used to form cell (cytology) blocks that incorporate the cell bed. The cell bed can be an inert cell bed of paraffin.

RELATED APPLICATIONS

This application is a divisional of U.S. application Ser. No.14/410,707, filed Dec. 23, 2014, which is a 35 U.S.C. 371 National PhaseApplication of PCT/US2013/047619, filed Jun. 25, 2013, which claimspriority to and the benefit of U.S. Provisional Application Serial No.61/664,985, filed Jun. 27, 2012, the contents of each of which arehereby incorporated by reference as if recited in full herein.

FIELD OF THE INVENTION

This invention relates to cell pathology tubes for cell collectionand/or processing.

BACKGROUND OF THE INVENTION

Compared to core or open biopsies, fine needle aspirates (FNA) are aquick and relatively safe method of biopsy to provide samples forevaluation of clinically suspicious mass lesions. FNA are often a firststep in evaluating whether a patient has a malignancy. Routinecollections during FNA include paired smears (Diff-Quick and H&E) andcell block (clot block or cell disk). Each collection is from a singlepass or aspiration. The paired smears are routinely performed on most ofthe passes to rapidly evaluate the morphology of the suspicious lesion.The cell block is used to process the specimen in a manner to allow forancillary testing. For example, the cell block can be used to evaluateimmunohistochemistry, FISH, PCR and the like, as well as to assessmorphology. The morphology of blocks may be diagnostically complimentaryin that they often provide more data with regard to the architecturalarrangement of cells compared to smears. The evaluation of cells fromFNAs typically employs very limited cell material. It is a known problemthat the quality of the cell block can deteriorate compared to pairedcell smears from the same procedure. Unfortunately, this deteriorationcan impair additional, sometimes confirmatory, testing or analysis thatcan be carried out on the specimen. This can result in an inconclusivediagnosis typically requiring additional diagnostic procedures atincreased risk and/or cost to the patient and may delay specifictherapy.

In the past, the cell blocks have been prepared using samples that areexpelled onto glass slides and placed in formalin within a short timeframe. The cell block is allowed to “clot” together to make a relativelysolid specimen that can be processed to make formalin-fixed paraffinembedded (FFPE) tissue samples. This cell block preparation process canresult in undue cell loss resulting in decreasing (and sometimes no)cell yields in the FFPE tissue samples.

SUMMARY OF EMBODIMENTS OF THE INVENTION

Embodiments of the invention provide tubular devices with integratedcell beds (e.g., paraffin beds) that can directly receive cells from aFNA or other sources at a collection site without requiring the use of aglass slide.

Embodiments of the invention provide tubular devices that can be usedfor the collection, transfer and subsequent centrifuge processing oftissue samples to form a cell block with suspended cells.

Aspects of the invention are directed to methods of collecting andprocessing a biosample. The methods include: (a) providing a tubularcontainer with an internal cavity having a cell bed residing above aclosed bottom end of the container; (b) inserting a biosample comprisingcells into the tubular container so that cells reside on the cell bed;(c) placing the tubular container with the cell bed and biosample in acentrifuge; (d) centrifuging the biosample in the tubular container sothat cells from the biosample deposit as a pellet against the cell bed;(e) inserting a liquid matrix material in the tubular container abovethe cell bed; (f) forming a solid cell block of the liquid matrixmaterial holding distributed cells therein above the cell bed; and (g)removing the solid cell block with the cell bed from the tubularcontainer.

The cell bed can be a solid, shape-changeable, moldable material that isable to change in shape in response to forces above those applied duringthe centrifuging step and can retain that shape during the inserting,centrifuging, forming and removing steps.

The cell bed can include solid paraffin and extends across the tubularcontainer.

The cell bed can have a middle portion with a substantially conicalshape that merges into an outer cylindrical upwardly extending outerportion that conformably attaches to an inner surface of a sidewall ofthe tube and the cell bed defines a closed solid cell bed surface.

Inserting the biosample can be carried out by depositing cells from afine needle aspirate directly from a needle holding the aspirate ontothe cell bed.

Placing the tubular container in the centrifuge can optionally becarried out by first placing the tubular container holding the biosampleon the cell bed in a coupler, adapter or larger tube forming acentrifuge assembly, then placing the assembly in a bucket of thecentrifuge and centrifuging the assembly.

The cell block can include cells from a fine needle aspirate tissuesample. The method can include, before the centrifuging step, invertingthe tubular container with the cell bed, then attaching the tubularcontainer to an open end of an elongate body comprising a liquid, theninverting the tubular container with the cell bed while attached to theelongate body with the liquid so that the cell bed is at a lower end ofthe tubular container, then centrifuging the biosample in the tubularcontainer.

Other embodiments are directed to cell pathology containers. Thecontainers can have a tubular body having an open interior space andopen opposing first and second end portions. A base is removablyattached to the second end portion of the tubular body. A solid cell bedresides in the tubular body proximate the base.

The cell bed can have a substantially planar bottom.

The cell bed can have a solid, shape-changeable, moldable material thatis able to retain a defined conical or frustoconical shape.

The cell bed can include solid paraffin and extend across the tubularcontainer to define a closed cell bed surface.

The cell bed can have a middle portion with a substantially conicalshape.

The cell bed can have a middle portion that merges into an outercylindrical upwardly extending outer portion that conformably attachesto an inner surface of a sidewall of the tube and the cell bed candefine a closed solid cell bed surface.

The solid cell bed can be pre-formed in the tubular body and/or base andcan define a closed solid cell bed surface, and wherein the container isenclosed in sterile packaging.

The base can include an internal substantially planar surface that holdsthe cell bed.

The base can hold a spacer that rises above a lower portion of the baseand extends into the tubular body, and the spacer can include an uppersubstantially planar surface that holds the cell bed.

The base can include an annular recess that surrounds the planar surfaceand engages a lower portion of the tubular body.

The tubular body first portion can releasably attach to either or bothof a cap or elongate body having a length that is greater than that ofthe tubular body.

The base and cap can have respective ledges of substantially commondiameter that extend radially outward from a centerline of the containerto reside a distance beyond a diameter of the tubular body.

The container can have a volume that is between about 10 mL to about 100mL. The tubular body has threads on upper and lower portions thereof,the lower portion configured to threadably attach to the base.

The tubular body can be sterile and configured to hold human or animalcell samples.

The first end portion of the tubular body can be attached to an open endof the elongate body. The elongate body can have a tapered segment thatmerges into a lower segment having a greater outer diameter. Theelongate body can have a removable end cap on an end opposing the openend.

Embodiments of the invention provide cell disks that can be used to makepathology or diagnostic specimens, e.g., surgical pathology FFPEspecimens from any kind of cellular source, e.g., suspension. Thisapplies to body fluids (pleural, pericardial, lung washing, etc.). Thesefluids have diagnostic utility, but also might be the only specimen incertain cases.

Special stains for amyloid or microorganisms can also be performed onany collected specimen, e.g., any FFPE specimens. This can be adapted tofluids for diagnosis.

Other aspects are directed to methods of collecting a biosample. Themethods include: (a) providing a tubular container with an internalcavity having a pre-formed solid paraffin cell bed residing above aclosed bottom end of the container; (b) inserting a needle with a fineneedle aspirate sample comprising cells into the tubular container sothat cells reside on the cell bed; and either (c)(i) placing a cap onthe container before or after inserting the biosample or (c)(ii)attaching the tubular container with the cell bed on an upper portion ofan elongate body with liquid and cells from other passes of FNA.

Yet other methods are directed to methods of processing a biosample. Themethods include: (a) obtaining a tubular container with an internalcavity having a solid cell bed residing above a closed bottom end of thecontainer and a biosample comprising cells that reside on the cell bed,wherein the tubular container with the solid cell bed and biosample isobtained from a collection site; (b) centrifuging the biosample in theobtained tubular container so that cells from the biosample deposit as apellet against the cell bed; (c) inserting a liquid matrix material inthe tubular container above the cell bed; (d) forming a solid cell blockof the liquid matrix material holding distributed cells therein abovethe cell bed; and (e) removing the solid cell block with the cell bedfrom the tubular container.

Still other aspects of the invention are directed to methods of makingcell beds for cell pathology containers. The methods include formingsolid paraffin into a defined cell bed shape so that the cell bed has amiddle portion with a substantially conical or frustoconical shape thatmerges into an outer cylindrical upwardly extending outer portion thatconformably attaches to an inner surface of a sidewall of the tube andthe cell bed defines a closed solid cell bed surface.

The tubular container holding the biosample on the cell bed can includean elongate body attached to an upper end thereof The elongate body caninclude liquid with supplemental cells from needles used to obtainadditional fine needle aspirates of target tissue corresponding to thebiosample on the cell bed. The centrifuging can be carried out to form apellet of the biosample cells and the supplemental cells.

It is noted that aspects of the invention described with respect to oneembodiment, may be incorporated in a different embodiment although notspecifically described relative thereto. That is, all embodiments and/orfeatures of any embodiment can be combined in any way and/orcombination. Applicant reserves the right to change any originally filedclaim or file any new claim accordingly, including the right to be ableto amend any originally filed claim to depend from and/or incorporateany feature of any other claim although not originally claimed in thatmanner. These and other objects and/or aspects of the present inventionare explained in detail in the specification set forth below.

Other systems and/or methods according to embodiments of the inventionwill be or become apparent to one with skill in the art upon review ofthe following drawings and detailed description. It is intended that allsuch additional systems, methods, and/or devices be included within thisdescription, be within the scope of the present invention, and beprotected by the accompanying claims.

BRIEF DESCRIPTION OF THE DRAWINGS

Other features of the present invention will be more readily understoodfrom the following detailed description of exemplary embodiments thereofwhen read in conjunction with the accompanying drawings.

FIG. 1A is a schematic illustration of a biosample container with anintegrated cell bed according to embodiments of the present invention.

FIG. 1B is a section view of a portion of a biosample container with anexample of a shaped cell bed according to embodiments of the presentinvention.

FIGS. 2A-2C are schematic illustrations of an exemplary sequence of cellcollection operations that may be used with biosample containersaccording to embodiments of the present invention.

FIGS. 3A-3F are schematic illustrations of an exemplary sequence of cellprocessing operations that can be carried out using the biosamplecontainers according to embodiments of the present invention.

FIGS. 4A-4C are schematic illustrations of an exemplary sequence ofpost-processing, cell block removal operations that can be carried outaccording to embodiments of the present invention.

FIG. 5 is a schematic illustration of a finished cell block (e.g., celldisk) on the cell bed in the containers shown in FIGS. 2A, 3A and 4Aaccording to embodiments of the present invention.

FIG. 6A is a partial exploded view of another example of a containeraccording to embodiments of the present invention.

FIG. 6B is a section view of another example of a container according toembodiments of the present invention.

FIG. 6C is an exploded schematic illustration of an exemplary containerwith interchangeable tubular bodies according to embodiments of thepresent invention.

FIG. 6D is an exploded schematic illustration of another exemplarycontainer with stackable container segments according to embodiments ofthe present invention.

FIG. 7A is a side perspective view of another example of a biosamplecontainer according to embodiments of the present invention.

FIG. 7B is a side view of the device shown in FIG. 7A.

FIG. 7C is a top view of the device shown in FIG. 7A.

FIG. 7D is a bottom view of the device shown in FIG. 7A.

FIG. 7E is a section view taken along lines 7E-7E in FIG. 7A.

FIG. 8A is a front view of a container assembly that holds a collectioncontainer with the integrated cell bed therein according to embodimentsof the present invention.

FIG. 8B is a front perspective view of the container assembly shown inFIG. 8A.

FIG. 9A is a front view of a biosample tube having an alternate top orcap configuration according to embodiments of the present invention.

FIG. 9B is a sectional view of the device shown in FIG. 9A.

FIG. 9C is a front view of a biosample tube similar to that shown inFIG. 9A, having an alternate top configuration for processing accordingto embodiments of the present invention.

FIG. 9D is a sectional view of the biosample tube shown in FIG. 9C.

FIG. 10A is a front perspective view of the container assembly (sansupper lid) adjacent an exemplary centrifuge according to embodiments ofthe present invention.

FIGS. 10B and 10C are top perspective views of the container in positionin the centrifuge according to embodiments of the present invention.

FIG. 11 is a schematic exploded view of a container according toembodiments of the present invention.

FIG. 12 is a schematic illustration of a container with an example of analternate lid configuration according to embodiments of the presentinvention.

FIG. 13A is a top perspective view of an exemplary mold for creatingformed cell beds according to embodiments of the present invention.

FIG. 13B is a schematic illustration of another forming apparatusaccording to embodiments of the present invention.

FIG. 13C is a section view taken along lines 13C-13C in FIG. 13A.

FIG. 14 is a schematic partial section view of yet another cell bedforming device according to embodiments of the present invention.

FIGS. 15A-15I are schematic illustrations of a sequence of operationsthat may be used to carry out embodiments of the invention and alsoillustrating another embodiment of a container according to embodimentsof the present invention.

FIG. 16 is a flow chart of exemplary operations that can be used toprocess cells according to embodiments of the present invention.

FIGS. 17-27 are digital photographs of exemplary processing steps usinga collection and processing container with an integrated cell bedaccording to embodiments of the present invention.

DETAILED DESCRIPTION OF EMBODIMENTS OF THE INVENTION

The present invention now is described more fully hereinafter withreference to the accompanying drawings, in which embodiments of theinvention are shown. This invention may, however, be embodied in manydifferent forms and should not be construed as limited to theembodiments set forth herein; rather, these embodiments are provided sothat this disclosure will be thorough and complete, and will fullyconvey the scope of the invention to those skilled in the art.

Like numbers refer to like elements throughout. In the figures, thethickness of certain lines, layers, components, elements or features maybe exaggerated for clarity. Broken lines illustrate optional features oroperations unless specified otherwise. One or more features shown anddiscussed with respect to one embodiment may be included in anotherembodiment even if not explicitly described or shown with anotherembodiment

The terminology used herein is for the purpose of describing particularembodiments only and is not intended to be limiting of the invention. Asused herein, the singular forms “a”, “an” and “the” are intended toinclude the plural forms as well, unless the context clearly indicatesotherwise. It will be further understood that the terms “comprises”and/or “comprising,” when used in this specification, specify thepresence of stated features, integers, steps, operations, elements,and/or components, but do not preclude the presence or addition of oneor more other features, integers, steps, operations, elements,components, and/or groups thereof As used herein, the term “and/or”includes any and all combinations of one or more of the associatedlisted items. As used herein, phrases such as “between X and Y” and“between about X and Y” should be interpreted to include X and Y. Asused herein, phrases such as “between about X and Y” mean “between aboutX and about Y.” As used herein, phrases such as “from about X to Y” mean“from about X to about Y.”

Unless otherwise defined, all terms (including technical and scientificterms) used herein have the same meaning as commonly understood by oneof ordinary skill in the art to which this invention belongs. It will befurther understood that terms, such as those defined in commonly useddictionaries, should be interpreted as having a meaning that isconsistent with their meaning in the context of the specification andrelevant art and should not be interpreted in an idealized or overlyformal sense unless expressly so defined herein. Well-known functions orconstructions may not be described in detail for brevity and/or clarity.

It will be understood that when an element is referred to as being “on”,“attached” to, “connected” to, “coupled” with, “contacting”, etc.,another element, it can be directly on, attached to, connected to,coupled with or contacting the other element or intervening elements mayalso be present. In contrast, when an element is referred to as being,for example, “directly on”, “directly attached” to, “directly connected”to, “directly coupled” with or “directly contacting” another element,there are no intervening elements present. It will also be appreciatedby those of skill in the art that references to a structure or featurethat is disposed “adjacent” another feature may have portions thatoverlap or underlie the adjacent feature.

Spatially relative terms, such as “under”, “below”, “lower”, “over”,“upper” and the like, may be used herein for ease of description todescribe one element or feature's relationship to another element(s) orfeature(s) as illustrated in the figures. It will be understood that thespatially relative terms are intended to encompass differentorientations of the device in use or operation in addition to theorientation depicted in the figures. For example, if the device in thefigures is inverted, elements described as “under” or “beneath” otherelements or features would then be oriented “over” the other elements orfeatures. Thus, the exemplary term “under” can encompass both anorientation of over and under. The device may be otherwise oriented(rotated 90 degrees or at other orientations) and the spatially relativedescriptors used herein interpreted accordingly. Similarly, the terms“upwardly”, “downwardly”, “vertical”, “horizontal” and the like are usedherein for the purpose of explanation only unless specifically indicatedotherwise.

It will be understood that, although the terms first, second, etc. maybe used herein to describe various elements, components, regions, layersand/or sections, these elements, components, regions, layers and/orsections should not be limited by these terms. These terms are only usedto distinguish one element, component, region, layer or section fromanother region, layer or section. Thus, a first element, component,region, layer or section discussed below could be termed a secondelement, component, region, layer or section without departing from theteachings of the present invention. The sequence of operations (orsteps) is not limited to the order presented in the claims or figuresunless specifically indicated otherwise.

The term “about” means that the recited number or value can vary by+/−20%.

The term “biosample” refers to human or animal tissue, blood or othersolid or liquid samples that have cellular material. The cellularmaterial can be limited cellular material, obtained from an FNA or otherspecimens including, for example, washings, lavages, and endoscopicprocedures. Embodiments of the invention can be used forimmunohistochemistry (IHC) or other studies including RNA and DNAanalysis, research or studies including FISH, PCR and the like and/or toassess morphology. Embodiments of the invention may be used with or forstains, such as “special stains” like Gram stains, Reticulin, Mucin andmay others as is well known to those of skill in the art.

Embodiments of the invention provide cell disks that can be used to makesurgical pathology FFPE specimens from any kind of suspension. Thisapplies to body fluids (pleural, pericardial, lung washing, etc.). Thesefluids have diagnostic utility, but also might be the only specimen incertain cases.

Special stains for amyloid or microorganisms can also be performed onany collected specimen, e.g., any FFPE specimens. This can be adapted tofluids for diagnosis.

Embodiments of the invention may be suitable for veterinarian use,medical human use or research for human and/or with laboratory animals.

The term “sterile” means that the noted device or material meets orexceeds defined medical guidelines of cleanliness and is substantially(if not totally) without contaminants so as to be suitable for medicaluses (e.g., diagnosis).

Turning now to the figures, FIG. 1A illustrates a cell collection tube10 with a base 11, an internal cavity 10 c and an internal cell bed 20held proximate the bottom 10 l of the tube 10. The cell bed 10 can be aninert cell bed. The term “inert cell bed” refers to a solid materialthat can support processed cell material above the base 11, typically ina block form, while preserving the cells, typically without chemicallyinteracting with the cells. Post collection and after processing, thecell bed 20 with patient cells C can be removed, substantially intact,e.g., scraped, pushed or otherwise disengaged from the base 11 withoutdisrupting the collected cells thereon for cell evaluation.

As shown in FIG. 1A, the cell bed 20 can be substantially planar (e.g.,the top and bottom can be flat similar to a flat block). As shown inFIG. 1B, the cell bed 20 can have an upper portion 20 u with a definedthree-dimensional body shape 20 s. The body shape 20 s can include asubstantially conical or frustoconical center portion 20 c forfacilitating cell collection during centrifugation. The center portion20 c can taper to have a valley that holds the cells/pellet 100. Thecell bed 20 can extend across an entire interior cavity space 10c at thebottom portion of the tube 10 l to define a closed surface cell bedabove the base 11. In some embodiments, the cell bed 20 can include anupwardly extending outer sidewall 20 w that rises a distance above thelaterally extending portion and conforms to the inner surface 10 i ofthe tube sidewall 10 w at the bottom portion of the tube 10 l. The outerperimeter sidewalls 20 w can inhibit some samples from being attractedto hydrophilic plastic (polymer) walls of the cylinder 10 b that canfacilitate forming the cell plug in the desired cell disk or block form.In addition, or alternatively, the taller walls 20 w can stay with thecylinder body 10 b when separated from the base 11, with the lowerportion of the cell bed 20 intact and remaining attached to the walls 20w. In other embodiments, the cell bed walls 20 w may detach from thelower cell bed 20 when the base 11 is removed.

In some embodiments, the tube body 10 b, base 11 and cap 12 can comprisea molded polymeric material that is sterilized for use. The tube body 10b, base 11 and/or cap 12 may also comprise other suitable materials,including, for example, glass.

In some embodiments, the cell bed 20 has a lower surface 20 s that canbe substantially planar 20 p. The base 11 can also have an internalsurface 11 i that is substantially planar. However, the base surface 11i can have other shapes and may include narrow channels or slots or caninclude “waves” or dimples and the like. The surface 11 i can beconfigured to allow for ease of removal of the cell bed 20 with cells ina “cell block” form 100 (FIGS. 4A, 4B), post-processing. The cell bedlower surface 20 s can reside against the base surface 11 i or mayreside a distance above the base 11 attached to an inner surface 10 s ofa sidewall 10 w of the tube 10.

The internal base surface 11 i can include a non-stick material and/orcoating that reduces sliding friction and/or otherwise facilitates theremoval of the cell bed 20 from the base 11 with the cell block 100(FIG. 4C) for conventional cell evaluation after processing. In someembodiments, the cell bed 20 with the cell block 100 can be pushed offthe base or pushed up and out of the tube body once the base is removed.Optionally, a thin flexible liner 110 (FIG. 4C) can reside on thesurface 11 i to allow the cell block 100 to be lifted or more readilyslid off the base 11 (FIG. 4C). The liner 110, where used, can beadhesively attached to the internal surface of the base 11 i and a usercan lift to peel an edge and dislodge the cell block 100.

The cell bed 20 can be a monolithic solid layer of an inert material. Inother embodiments, the cell bed 20 can comprise a plurality of stackedlayers of different solid materials or a mixture of materials. The cellbed 20 can comprise paraffin or other suitable material alone or incombination with one or more other materials. In some embodiments, thecell bed 20 is defined by a monolithic paraffin body. In someembodiments, DNase and/or RNase inhibitors may be added to the fixativeor other liquid solutions and/or paraffin that may improve futuremolecular testing.

In some embodiments, the base 11 is detachable, e.g., releasablyattachable to a bottom portion 10 l of the tube 10. This releasableattachment can be by any suitable attachment configuration including,for example, threaded attachment, bayonet or frictional fit, snap fit,hooks, VELCRO, adhesive attachment, frangible attachments, any of whichmay optionally also employ O-rings, compatible sealant, wax or grease orwashers to promote a sufficient fluid-tight seal. For frangibleattachments, the tube body 10 b and/or base 11 can be integrallyattached and configured to preferentially tear or detach about a definedzone when exposed to sufficient compressive, torsion or tensile forces.

The tube 10 can be provided in a sterile package 40 for onsitecollection of a specimen from a patient. The term “onsite” refers to acollection location of a patient such as a surgical or biopsy room,doctor's office or hospital or laboratory site. The tube 10 can includea lid or cap 12 (FIG. 2C) that is provided in the package 40 or in aseparate package. In other embodiments, non-sterile uses arecontemplated.

The base 11 can be provided in the package 40 pre-assembled orpre-formed in the tube 10 and/or base 11 as shown. Alternatively, it maybe provided separately for attachment at the use (collection) site (FIG.11). As such, the cell bed 20 may be provided as a separate component inthe package 40 or a separate package (held in a rigid container so as toprotect the preformed shape). In other embodiments, the cell bed 20 ispre-assembled into the base 11 or bottom 10 l of the tube body 10 b. Insome particular embodiments, the cell bed 20 can be formed in the tube10 at the collection site if a suitably reliable press or formationsystem can be included in a collection kit.

In some embodiments, the cell bed 20 can be pre-formed in the tube 10with a defined three-dimensional shape, in package 40, so that the tube10 is ready for use at a cell collection site. The package 40 can hold asingle tube or multiple tubes 10. The cap 12 (FIG. 2C) can be on therespective tube 10 to maintain the sterility until use. FIGS. 2A-2Cillustrate exemplary steps that can be carried out at a collection siteto collect cells for subsequent evaluation. As shown in FIG. 2A, asample with cells C is introduced into the internal cavity 10 c of thetube 10 and rest on the cell bed 20. The cells C may comprise aspiratedcells (unclotted) from a FNA using a needle 75 that is directly insertedinto the tube 10, in some embodiments. FIG. 2B illustrates that thecells C may then clot (onsite). FIG. 2C illustrates that a supernatant,e.g., a solution of fixative liquid 15 that may comprise formalin orother suitable fixative material such as Zinc can be introduced into thetube 10. Other fixatives may include, but are not limited to, saline,alcohols, acetone, mercury based reagents, and even media (Lennox broth,RPMI, etc.). The vessel 10 can be provided unfilled and a user canselect the appropriate fixative or several or a particular type may beprepackaged in a kit which may be ordered for use. Any media used in thetube body 10 b should be sterilized.

A lid 12 can be attached to the tube 10 and transported or stored. Asshown, there may be undesired floating cells F in the solution above theclotted cells on the cell bed 20.

The lid 12 can be a rigid closed lid that is attached after the fixative15 is introduced. However, in some embodiments the lid 12 can include aliquid entry port to allow the liquid to enter while the lid remains on.The lid 12 can include a luer lock or luer slip connection fitting thatengages with a male syringe luer lock or slip fitting to provide theliquid entry hat allows the liquid to be introduced through the port.

FIGS. 3A-3F illustrate steps that can be carried out at a cytologylaboratory or other suitable research or clinical laboratory. FIG. 3Ashows the tube 10 after centrifugation in a centrifuge 200 (FIG. 10).The centrifuge can be a standard laboratory centrifuge, typically a lowspeed centrifuge that permits the separation of the fixative from thecells and allows the cells to form a cell pellet P as is known to thoseof skill in the art. The centrifuge may be configured to processstandard 50 mL or 100 mL conical tubes and the tube 10 can be placedtherein alone or with an adapter. That is, the tube 10 may include asleeve, adapter, or coupler or may have an external integrated sizeand/or design that allows it to be placed directly into the “bucket” orstandard receptacle of the centrifuge.

The fixative liquid 15 is removed (e.g., the formalin is decanted) asshown in FIG. 3B and a rinse solution 18 can be added to the tube 10 asshown in FIG. 3C. The fixative liquid 15 can be removed and the rinse 18added via any suitable technique that leaves the cells C and/or pellet Pin the tube 10 including aspiration tubing, pipette withdrawal,decanting and the like. Typically, the supernatant should be aspiratedgently with a vacuum rather than being decanted (which refers to tippedand poured) to minimize or reduce trauma to the cell pellet. As before,the rinse solution or other liquids can be removed or added with the lid12 off as shown in FIG. 3B or with the lid remaining on the tube using aliquid entry and/or retraction port. It is also contemplated thatdifferent lids having the same or different configurations may be usedat different points in the process.

In some embodiments, a clot blot formed during thecollection/post-collection can be used as a cap for a rinse vessel.

FIG. 3D illustrates that the tube 10 with the rinse 18 can then becentrifuged. FIG. 3E illustrates that the rinse 18 can be decanted orotherwise removed or withdrawn, leaving cells C on the cell bed 20,typically in pellet form P. FIG. 3F illustrates that a matrix material28 can be added to form a cell block 100. The term “matrix material”refers to a specimen-processing gel (that may be aqueous) thatencapsulates and suspends histologic and cytologic specimens in asolidified medium. The matrix material 28 can include one or more ofagar, agarose gel or “histogel” solid at ambient temperature,Methocell®, Matrix Gel®, OCT compounds, paraffin, denatured andnon-denatured collagen, fibronectin, laminin, plasma and thrombin andother mixtures. Other matrixes for cell immobilization can also be used.For a discussion of cell blocks and ethanol formalin fixative and otherfixatives, see, e.g., Nathan et al., Improved Preparation and ItsEfficacy in Diagnosing Cytology, Am J Clin Pathol, 2000; 1114, 599-606,the contents of which are hereby incorporated by reference as if recitedin full herein.

FIG. 4A illustrates that the base 11 and body of the tube 10 b aredetached from each other, exposing the cell block 100 on the cell bed20. The cell block 100 with the cell bed 20 are removed from the base 11as shown in FIG. 4B. The cell block 100 with cell bed 20 can bedetached, removed or separated in any suitable manner including, forexample, scraping, sliding or lifting (e.g., using a liner 110, FIG.4C).

FIG. 5 illustrates the resulting cell block 100 (also termed cell disk)that includes the cell bed 20 ready for routine processing. The cellblock 100 can be sliced or cut for preparing slides for staining orother diagnostic protocols. There may be an increased number of cells inthe cell block or slices thereof that may promote diagnostic capabilityover smears alone.

FIG. 6A illustrates the tube 10 with the base 11 detached from the tubebody 10 b. In this example, the base 11 includes a raised centerpedestal 11 p that forms the inner surface 11 i that holds the cell bed20. The perimeter of the pedestal 11 p can include threads that engagean inner surface of the tube body or may frictionally engage the tubebody using seals such as an O-ring(s) and the like (not shown).Typically, the base 11 with the cell bed 20 on the pedestal is attachedto the tube body 10 b and packaged for use at a collection site.

FIG. 6B illustrates that the tube 10 can include a spacer 13 that risesa distance above the lower portion of the base 11. FIG. 6B alsoillustrates that the base 11 can attach to the tube body 10 b at alocation above the bottom of the base 11. The spacer 13 can include asubstantially planar or flat surface for holding the cell bed 20. Thebase 11 and tube body 10 b can threadably couple together. In theembodiment shown, the base 11 includes external threads 34 and the tubebody 10 b includes internal threads 38. However, as noted above, othercoupling configurations may be used.

FIG. 6C illustrates that the base 11 can interchangeably attach to twodifferent tube bodies 10 b ₁, 10 b ₂, and/or the different tube bodiescan have different volumes. Thus, for example, the smaller tube body 10b ₁ can be used at the collection site and for transport to the cytologylab. The larger tube body 10 b ₂ can be used at the cytology lab forprocessing in the centrifuge, for example. The same or differentlyconfigured caps or lids 12 may be used for each tube body 10 b ₁, 10 b₂. In other embodiments, different volume tube bodies 10 b ₁, 10 b ₂ canbe provided in a package and selected for use at the collection siteallowing for increased flexibility corresponding to the specimen type(e.g., urine, blood plasma or serum versus FNA).

FIG. 6D illustrates that the tube body 10 b can include several segments10 b ₁, 10 b ₂ that attach together to provide a different volumetriccapacity. Thus, for example, one segment 10 b ₁ can be attached and usedwith the cap or lid 12 at the collection site and for transport. Thelid/cap 12 can be removed and the second body 10 b ₂ can be attached tothe first body 10 b ₁ at the cytology lab and the stacked segments candefine the tube body 10 b used for centrifugation. Where more than onetube body segment 10 b ₁, 10 b ₂ is used, one or both can be detachedfrom each other and/or the base 11 to expose the cell bed 20 with thecell block 100 for access/removal of the cell block 100 for subsequentprocessing and analysis.

FIG. 7A is an exploded view of another example of a tube 10. In thisexample, the base 11 has an annular open space 33 with female threads 34that surrounds the internal surface 11 i that holds the cell bed 20. Thefemale threads 34 matably engage external male threads 38 on the bottomportion of the tube 10 l.

FIGS. 7B-7E illustrate that the tube 10 can include top and bottomindicia 12 m, 11 m so that a user knows which end is “up” before usingor opening. In some embodiments, a visually transparent window may beprovided in the tube or cap or base or the device may be transparent ortranslucent. The cell bed 20 can have a substantially conical shape withthe lowest peak facing the base 11 along an axially projectingcenterline of the tube body 10 b. The outerwalls of the cell bed 20 wcan extend above the center portion of the cell bed 20 in asubstantially straight vertical orientation so as to conform to thesidewalls of the tubular body 10 b. The sidewalls 20 w can cover morethan a major portion (e.g., greater than 50%) of the enclosed fluidcavity 10 c, leaving a minor portion of the sidewalls 10 w of the tubebody 10 b below the cap 12 free of the cell bed material.

The tube 10 can have a defined capacity or volume. The tube 10 may havea volume or capacity between about 10 mL to about 200 mL, includingabout 20 mL, about 30 mL, about 40 mL, about 50 mL, about 60 mL, about70 mL, about 80 mL, about 90 mL, and about 100 mL. The tubes 10 can beprovided in different volumes/sizes for different applications. Wheretwo segments 10 b ₁, 10 b ₂ are used, one can have a volume between 10mL to 25 mL and the other can have a volume between 25 mL and 100 mL,for example.

The lid 12 can also be threadably attached to an upper portion of thetube body 10 via threads 12 t, 138. The base 11 and cap 12 can have aledge 39, 139 with a diameter that defines a tight fit with a receptacleof a standard centrifuge or with a standard tube, sleeve or otheradapter allowing the tube 10 to be placed in a centrifuge forprocessing.

The cap and base ledges 39, 139 can be configured to have the same outerdiameter size. The outer perimeter of the ledge can include a pattern ofcircumferentially spaced apart recesses or grooves 39 g, 139 g. Theledges 39, 139 can provide a resilient fit to provide for snugengagements using an overcoat, outerlayer or substrate of resilientmaterial or just based on the groove configurations.

In some embodiments, the tube 10 is sized and configured as a 50 mL tubeand can snugly engage a centrifuge receptacle without the use of anadapter or without a customized sleeve or other adapter.

FIGS. 8A and 8B illustrate that the tube 10 can be placed inside alarger (standard) tube 50 for standard centrifuge processing. The ledges39, 139 can snugly engage the sidewall of the tube 50. The tube 50 caninclude a cap 52 and the lower portion 54 can include a center with aconical internal shape 55. The tube 10 typically resides over theconical shape in the bottom portion of the standard tube 50. However,the tube 10 can be placed above this location as well. The tube 10 canbe slid in and out of the tube 50 for access.

FIGS. 9A and 9B illustrate another embodiment of a container 10′ wherethe tube body 10 b can releasably attach to an elongate body 150 whichmay be attached to a second cap 12 b. As shown, the elongate body 150 isin fluid communication with the tube fluid cavity 10 c. The second tubecap 12 b can define a fluid port 153 that allows fluid from the elongatebody 150 to be introduced or withdrawn. The tube body 10 b with thesecond cap 12 b can be configured to reside in a standard 50 mL tube 50as shown. In other embodiments, the tube body 10 b and second cap 12 bcan be configured to snugly reside in a centrifuge receptacle (e.g.,bucket) without requiring the tube 50. The elongate body 150 can beintegral with the tube cap 12 b, e.g., a monolithic molded unitarycomponent. In other embodiments, the elongate body can be configured toattach to the lid 12 b in other ways including threaded, snap fit andthe like, while providing a fluid-tight seal. FIGS. 9C and 9D illustratea similar configuration of a container 10′ with an alternate topconfiguration. In some embodiments, the elongate body 150 may beattached at the collection site as the original cap. In otherembodiments, a cap or lid 12 such as that shown in FIG. 7A can be usedat the collection site and/or for shipment and transport and the secondcap 12 b or elongate body 150 interchanged later for processing.

FIG. 10A shows the tube 10 sitting over a spacer 30 snugly attached toand in a standard 50 mL tube 50 in preparation for centrifugation in abucket 210 of the centrifuge 200. FIG. 10B illustrates the tube 10 inthe tube 50 in a standard swing bucket 210 of the centrifuge 200. FIG.10C illustrates centrifugation with the tube 10 on its side (andhorizontal) rather than angled so that the specimen is collected in amiddle 20 c (FIG. 1B) of the cell bed 20.

FIG. 11 illustrates the components of a tube 10 according to someembodiments. As noted above, the cell bed 20 can be pre-formed andprovided for assembly onsite or may be pre-attached to the base 11and/or tube body 10 b. Typically, the base 11 with the cell bed 20 isattached to the tube body 10 b and packaged for use at a collectionsite.

FIG. 12 illustrates that the cap 12′ can be configured to engage aleur-lock of a syringe 120 for introducing and/or removing differentliquids.

FIGS. 13A and 13C illustrate examples of a mold that has mold cavities20 c ₁-20 c _(n) that can concurrently form a plurality of cell beds 20.Cell bed material, in liquid, solid, or semi-solid form, typically inflowable (fluid or gel) form can be introduced into the mold via one ormore mold ports or through an open access region and molded into thepre-formed cell bed shape for use in the tube 10.

In some embodiments as shown in FIG. 13B, a mechanical press 251 withshaped mold members 253 can be configured to enter the tube body 10 bwith an attached base 11 held in a lower holding member 252 to allowconcurrent cell bed formation in multiple tubes 10. The cell bedmaterial 20 m can be inserted in solid or liquid form, typically in asolid, but perhaps slightly heated form for aid in formation of thedesired cell bed shape.

In other embodiments, as shown in FIG. 14, a respective cell bed 20 isformed directly in an attached base 11 and tube body 10 b using a shapedtamper tool 260.

In some embodiments, the tubes 10 can be used to process cells for humanor veterinary uses. In certain embodiments, the tubes 10 can be directedto preparation of cells for pathology review. While it is contemplatedthat the tubes 10 are particularly suitable for cells obtained by fineneedle aspiration, it should be clear to one of skill in the art thatcellular material captured by other means could also be collected andprocessed by the tubes 10.

Cell material could also be collected by endoscopy, including but notlimited to arthroscopy, bronchoscopy, colonoscopy, colposcopy,cystoscopy, ERCP (endoscopic retrograde cholangio-pancreatograthy), EGD(esophogealgastroduodensoscopy), endoscopic biopsy, gastroscopy,laparoscopy, laryngoscopy, proctoscopy and thoracoscopy. Cells couldalso be obtained from lavage procedures, including but not limited tobronchoalveolar, breast ductal, nasal, pleural, peritoneal,gastrointestinal, arthroscopic, and urinary bladder lavages. It is alsocontemplated that cells could be collected from catheters such as thoseused in infusion, cardiovascular, renal, bladder, urethral, hemodynamicmonitoring, neurological, and other procedures which would be obvious toone of skill in the art. In some embodiments, cell samples can be fromeye/cornea/globe aspirations, endocervical/ectocervical/endometrialcurettages, cyst aspirations and urine. It is also contemplated thatcell samples can be for xenografts from research and animal modeling aswell as patient directed therapy.

The cells can be from washings and spontaneously exfoliated specimensincluding bronchial washings, bronchoalveolar lavage, sputum pleuralfluid, pericardial fluid, peritoneal fluid, peritoneal washing, ovariancyst fluid, synovial fluid, urine, brain cyst fluid, cerebrospinalfluid. The cells can be for RNA/DNA research or analysis and may includelive cells. With the use of appropriate media, the tubes 10 can act as asmall incubator to keep cells alive (at least for a short period oftime). DNase/RNase inhibitors can be introduced to the media to alsopreserve DNA/RNA. As is known, fixation alone can help with DNA/RNApreservation.

In particular embodiments, the cell samples are from endocervicalcurettages (ECC). In the past, conventional practice when the firstslide from the original paraffin block is essentially noncontributory,is to take the fluid remaining in the specimen jar and perform a“ThinPrep” on it. These typically have many cells (squamous andglandular) but there is no architecture. Rather than place the minimalslime usually present in a specimen jar in a cassette, it iscontemplated that those cells can be put in the tubular body 10 b (or150, FIG. 9A, 15A) at the collection site. This should give betterinitial yield with architecture present and a source for immunos. Thislatter may not be inconsequential. For example, when the ECC contains aminute fragment of small cells with high N/C ratios, it is hard todiscern whether they are not relevant (being potentially from the loweruterine segment) or clump of HGSIL cells. A single immuno-p16—can bevery useful in this scenario. The term “immuno” and plurals thereofrefer to immunoperoxidase studies and include antibodies targetingspecific epitopes to aid in tumor/disease differentiation. Also known as(although technically incorrect) immunohistochemistry: p16 is aprotein/antigen with the p16 antibody in a cell having clinicalsignificance.

FIGS. 15A-15I illustrate another embodiment of a container 10″ similarto that shown in FIGS. 9A and 9B. In this embodiment, no external tubeis required for centrifuge processing. As shown, the container 10″includes a tube body 10 b holding the cell bed 20 and a base 11. Thecontainer 10″ also includes an elongate body 150 that can attach to thetube body 10 b. The elongate body 150 can include a first end with a lid155 and a second opposing end 157 that is open. As shown in FIG. 15A,the elongate body 150 can include a desired solution, such as saline orformalin 15. FIG. 15B illustrates that, as before, a FNA sample can beinserted onto the cell bed 20. One or more needles from other passesobtained from the target tissue can be rinsed in the chamber of theelongate body 150. This is in contrast to a jar filled with saline usedconventionally. As shown in FIGS. 15C and 15D, the tube body 10 b andbase 11 can be attached together after the pellet P is dried allowingthe tube body 10 b with cell bed 20 and pellet P to be inverted toattach to the open end 157 of the elongate body 150. The open end of theelongate body 157 can be sized and configured to be substantially thesame as the size of the upper end of the tube body. The elongate body157 can taper to a large size away from the open end as shown. The tubebody 10 b can engage the open end of the elongate body 157 in a fluidtight manner using appropriate seals, threads, frictional fits and thelike.

FIG. 15E shows that the container 10″ can be inverted so that the cellbed 20 is in the lower portion of the container 10″. The container 10″can be centrifuged at an appropriate revolution per minute and duration(e.g., about 2000 rpm for about 5 minutes) to form a combined pellet Pc(FIG. 15F) on the cell bed 20 (combined from cells collected from therinse solution and the FNA direct deposit). FIG. 15G illustrates thatthe supernatant can be aspirated as is conventional using a vacuumleaving only a minimal amount of fixative 15 (e.g., formalin or saline)in the tube body 10 b above the cell bed 20 so as to not disrupt thecell pellet P. The aspiration can be carried out by first removing lid155 or by using a sealed port in the lid (not shown). As shown in FIG.15H, the elongate body 150 can then be removed. A liquid matrix 28 canbe added to the tube body 10 b and cells resuspended. FIG. 15Iillustrates that the cell disk or block 100 with the cell bed 20 can beremoved from the tube body 10 b using, for example, a plunger 300. Thecell block 100 can be processed as a histology specimen or other desiredspecimen.

FIG. 16 is a flow chart of exemplary operations that can be used tocarry out embodiments of the invention. A cell sample can be placed in atube having a cell bed (block 350). The sample is centrifuged while inthe tube (block 360). A cell block is removed from the tube with thecell bed and solidified matrix holding the cells (block 370).

The cell sample can be placed with a needle with a fine needle aspiratesample directly in the tube (block 352). Liquid matrix material (e.g.,specimen-processing gel that encapsulates and suspends histologic andcytologic specimens in a solidified medium) can be added to the tubeafter the centrifuging and the matrix material with the cellsdistributed therein can be solidified to form the cell block (block365). The cell sample can be collected in the tube at a patientcollection site and the tube can be transported to a cytology lab forprocessing (block 355).

The base of the tube can be separated from the tube body to expose thecell block and allow the cell block to be removed with the cell bed(block 368).

In some embodiments, generally summarized, rinses can be performed inthe collection vessel 10 and the dedicated clot blot(s) can be generatedas discussed above. The clot blot can be used as a cap for the rinsevessel. The entire apparatus can be inverted (clot block side down) andcentrifuged. The supernatant can be aspirated leaving a clot blot withoverlaying precipitated materials (button). A desired amount (nottypically calculated precisely, but roughly, about 1:1/v:v to thebutton) of HistoGel can be pipetted onto the button and immediately spunagain in a centrifuge. This time the collection vessel is not needed.This allows the HistoGel to permeate the cells and polymerize. Again,this step is carried out quickly to prevent polymerization before thecentrifugation. This leaves the cells within a matrix of HistoGel. Thisaction can prevent loss of cells in downstream processing procedures.

The present invention is explained in greater detail in the followingnon-limiting Examples.

EXAMPLES

FIGS. 17-27 are digital images of an exemplary tube 10 and exemplaryprocessing that can be carried out using the tube (the centrifugeoperations were shown above with respect to FIGS. 10A-10C). FIG. 17illustrates a FNA expelled directly from a needle into the cell bed 20of the base 11 (which is attached to the tube body 10 b). As shown inFIG. 18, the cell sample C can settle in the middle of the cell bed 20and/or base 12 due to the substantially conical or furstoconical shapeof the cell bed 20. The sample can be allowed to dry and/or coagulate.

The supernatant (formalin) is aspirated and discarded being careful notto disrupt the pelleted sample P as shown in FIG. 19. FIG. 20illustrates the tube 10 with a sample pellet P. Some supernatant mayremain but does not interfere with subsequent processing.

After placing the tube 10 in the tube 50, and centrifuging (as describedabove), liquid histogel (melted agarose) can be pipetted up and down inthe tube 10 as shown in FIG. 21 using pipette 299 to resuspend thesample in the histogel. About 30 μL of agarose may be used for thisresuspension although other amounts may also be appropriate. FIG. 22illustrates that the suspension can be carried out relatively rapidly sothat the agarose does not solidify. FIG. 23 shows the tube with thesuspended sample in a low temperature freezer (e.g., about −20C) tofacilitate solidification, which can occur in between about 2-5 minutes.

FIG. 24 illustrates the cell block 100 (e.g., the cell bed 20 and thesolid histogel with cells) being removed from the tube 10 b and/or base11. FIG. 25 shows that the cell bed 20 may attach to the inner wall ofthe tube body 10 b and may need a plunger or other push member 300 topush the cell bed with the cells, e.g., cell block 100 from the tubebody (typically out the top, pushing against the cell bed 20 rather thanthe cells/histogel (agarose) mixture 100.

FIG. 26 illustrates the cell block 100 with cell bed 20 placed onroutine tissue paper. As is known to those of skill in the art, it isstandard practice to wrap the sample 100 in tissue paper in preparationfor tissue processing for small histology specimens. FIG. 27 illustratesthe tissue paper wrapped cell block 100 with cell bed 20 in a standardhistology cassette 310. The darker dots inside the wrapped cell block100 are cells C.

Although shown as a manual operation, it is contemplated that machinesmay be used to automatically carry out certain of the above steps.

Table 1 below is a list of 15 cases of data comparing an exemplarycollection vessel with the standard methods. All cases were graded from1 (poor) to 2 (adequate) to 3 (superior). The first row is thediagnosis. The 2nd row is the paired smear quality (DQ and H&E). TheCBCS is the remnant material left on the traditional clotting slide. Theclot blot is the standard method compared to the cell disk method (CD).Last level was the last recut level on the FFPE block. The method wasoverall graded for superiority. As seen, the standard method was neversuperior to the new CD method but equivocal in some cases.

TABLE 1 DATA SUMMARY Smear Clot Blot Cell Disk Pathologic Quality CBCSQuality Quality Last Best Diagnosis (1-3) (1-3) (1-3) (1-3) Level MethodOncocytoma 2 2 1 2 3 CD RCC, clear cell 3 1 1 2 3 CD Pleomorphic 3 2 1 23 CD adenoma Large cell 3 3 3 3 3 Tied carcinoma Adenocarcinoma 3 2 3 35 Tied Scc 2 3 2 2 3 Tied Urothelial 3 2 2 1 3 CD carcinoma Invasiveductal 3 1 3 3 3 CD carcinoma Hodgkin 3 3 3 3 9 CD lymphoma RCC,papillary 2 n/a 3 3 3 CD Follicular 3 3 2 2 5 Tied adenoma Solid- 3 1 11 5 Tied pseuodopapillary Urothelial 2 1 1 2 3 CD carcinoma Oncocytoma 33 3 3 5 CD Scc 3 2 1 2 5 CD

The foregoing is illustrative of embodiments of the present inventionand is not to be construed as limiting thereof. Although a few exemplaryembodiments of this invention have been described, those skilled in theart will readily appreciate that many modifications are possible in theexemplary embodiments without materially departing from the novelteachings and advantages of this invention. Accordingly, all suchmodifications are intended to be included within the scope of thisinvention as defined in the claims. The invention is defined by thefollowing claims, with equivalents of the claims to be included therein.

That which is claimed:
 1. A method of collecting and processing abiosample, comprising: providing a tubular container with an internalcavity having a solid cell bed residing above a closed bottom end of thecontainer; inserting a biosample comprising cells into the tubularcontainer so that cells reside on the cell bed; placing the tubularcontainer with the cell bed and biosample in a centrifuge; centrifugingthe biosample in the tubular container so that cells from the biosampledeposit as a pellet against the cell bed; inserting a liquid matrixmaterial in the tubular container above the cell bed; forming a solidcell block of the liquid matrix material holding distributed cellstherein above the cell bed; and removing the solid cell block with thecell bed from the tubular container.
 2. The method of claim 1, whereinthe cell bed is a solid, shape-changeable, moldable material that isable to change in shape in response to forces above those applied duringthe centrifuging step and can retain that shape during the inserting,centrifuging, forming and removing steps.
 3. The method of claim 1,wherein the cell bed comprises solid paraffin and extends across thetubular container.
 4. The method of claim 1, wherein the cell bed has amiddle portion with a substantially conical shape that merges into anouter cylindrical upwardly extending outer portion that conformablyattaches to an inner surface of a sidewall of the tube and the cell beddefines a closed solid cell bed surface.
 5. The method of claim 1,wherein the inserting the biosample is carried out by depositing cellsfrom a fine needle aspirate directly from a needle holding the aspirateonto the cell bed.
 6. The method of claim 1, wherein the placing thetubular container in the centrifuge is carried out by first placing thetubular container holding the biosample on the cell bed in a coupler,adapter or larger tube forming a centrifuge assembly, then placing theassembly in a bucket of the centrifuge and centrifuging the assembly. 7.The method of claim 1, wherein the cell block comprises cells from afine needle aspirate tissue sample.
 8. The method of claim 1, furthercomprising replacing a first cap with a second cap holding an elongatebody thereabove with a fluid port in fluid communication with thetubular body internal cavity.
 9. The method of claim 1, furthercomprising, before the centrifuging step, inverting the tubularcontainer with the cell bed, then attaching the tubular container to anopen end of an elongate body comprising a liquid, then inverting thetubular container with the cell bed while attached to the elongate bodywith the liquid so that the cell bed is at a lower end of the tubularcontainer, then centrifuging the biosample in the tubular container. 10.A method of collecting a biosample, comprising: providing a tubularcontainer with an internal cavity having a pre-formed solid paraffincell bed residing above a closed bottom end of the container; insertinga needle with a fine needle aspirate (FNA) sample comprising cells intothe tubular container so that cells reside on the cell bed; and either(i) placing a cap on the container before or after inserting thebiosample or (ii) attaching the tubular container with the cell bed onan upper portion of an elongate body with liquid and cells from otherpasses of FNA.
 11. The method of claim 10, wherein the cell bed has amiddle portion with a substantially conical shape that merges into anouter cylindrical upwardly extending outer portion that conformablyattaches to an inner surface of a sidewall of the tube and the cell beddefines a closed solid cell bed surface.
 12. A method of processing abiosample, comprising: obtaining a tubular container with an internalcavity having a solid cell bed residing above a closed bottom end of thecontainer and a biosample comprising cells that reside on the cell bed,wherein the tubular container with the solid cell bed and biosample isobtained from a collection site; centrifuging the biosample in theobtained tubular container so that cells from the biosample deposit as apellet against the cell bed; inserting a liquid matrix material in thetubular container above the cell bed; forming a solid cell block of theliquid matrix material holding distributed cells therein above the cellbed; and removing the solid cell block with the cell bed from thetubular container.
 13. The method of claim 12, wherein the cell bed is asolid, shape-changeable, moldable material that is able to change inshape in response to forces above those applied during the centrifugingstep and can retain that shape during the inserting, centrifuging,forming and removing steps.
 14. The method of claim 12, wherein the cellbed comprises solid paraffin and extends across the tubular container.15. The method of claim 12, wherein the cell bed has a middle portionwith a substantially conical shape that merges into an outer cylindricalupwardly extending outer portion that conformably attaches to an innersurface of a sidewall of the tube and the cell bed defines a closedsolid cell bed surface.
 16. The method of claim 12, wherein, before thecentrifuging, the method includes placing the tubular container holdingthe biosample on the cell bed in a coupler, adapter or larger tubeforming a centrifuge assembly, then placing the assembly in a bucket ofthe centrifuge and centrifuging the assembly.
 17. The method of claim 12wherein the tubular container holding the biosample on the cell bedincludes an elongate body attached to an upper end thereof, the elongatebody comprising liquid with supplemental cells from needles used toobtain additional fine needle aspirates of target tissue correspondingto the biosample on the cell bed, and wherein the centrifuging iscarried out to form a pellet of the biosample cells and the supplementalcells.
 18. The method of claim 12, wherein the cell block comprisescells from a fine needle aspirate tissue sample.